Effect of iron and phagocytosis on murine macrophage activation in vitro
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Iron-exposed murine macrophages have a modified bactericidal activity as shown by previous observations. In order to assess the role of iron in macrophage activation, as measured by free radical production and by intracellular bacterial killing, murine peritoneal macrophages were cultivated in the presence of various sources of iron, human iron-saturated transferrin and ammonium ferric citrate, or iron chelators, Desferal, and human Apo-transferrin, and were infected with an enteropathogenic strain ofE. coli. The release of nitrite (NO2 −), and the production of superoxide anion (O2 −) and hydrogen peroxide (H2O2) by the phagocytes were measured and compared to the production by uninfected macrophages. The synergistic action with murine r.IFN-γ was also studied in the radical production reaction and for the bactericidal activity of macrophages. Our results show that in vitro phagocytosis ofE. coli induced elevated production of NO2 − and H2O2 by macrophages, and that oxygen derivatives were released independently of the presence of added iron or chelator. Despite a phagocytosis-related enhancement of NO2 − release, reactive nitrogen intermediates (RNI) are not directly involved in the bactericidal mechanism, as revealed by increased intracellular killing owing to RNI inhibitors. Moreover, bacterial killing may depend on oxygen derivatives, as suggested by the effect of the antioxidant sodium ascorbate leading to both a diminished H2O2 production and a decreased bactericidal activity of macrophages.
Index EntriesIron, Role of iron in macrophage activation Nitrite, hydrogen peroxide, superoxide anion production by infected macrophages role of free radicals in bactericidal activity of macrophages E. coli murine peritoneal macrophages
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- 2.R. A. Finkelstein, C. V. Sciortino, and M. A. McIntosh,Rev. Infect. Dis. 5, S759 (1983).Google Scholar
- 7.Y. Gauthier and P. Isoard,Biochem. J. 241, 273 (1987).Google Scholar
- 10.B. Halliwell and J. M. C. Gutteridge,Free Radicals in Biology and Medicine. Clarendon Press, Oxford (1989).Google Scholar
- 13.Y. Gauthier and P. Isoard,Pathobiol. 60 (S1), 9 (1992).Google Scholar
- 15.E. Pick, inMethods in Enzymology, vol. 132 (5), G. Di Sabato and J. Everse, eds., Academic Press, Orlando, FL, pp. 407–421 (1986).Google Scholar
- 25.D. M. Teale and A. M. Atkinson,J. Anti-microb. Chemother. 30, 839 (1992).Google Scholar
- 28.M. de Sousa, inIron in Immunity, Cancer and Inflammation, M. de Sousa and J. H. Brock, eds., John Wiley, Chichester, UK, pp. 247–258 (1989).Google Scholar
- 30.P. Elsbach and J. Weiss,Inflammation: Basic Principles and Clinical Correlates, 2nd ed., J. I. Gallin, I. M. Goldstein, and R. Snyderman, eds., Raven, New York, pp. 603–636 (1992).Google Scholar
- 32.K. Abok, T. Hirth, J. L. E. Ericsson, and U. Brunk,Virchows Arch. (Cell. Pathol.) 43, 85 (1983).Google Scholar